American Thyroid Association 87th Annual Meeting:

Measurement of serum thyroglobulin levels following surgery for differentiated thyroid cancer not only provides information about the presence or absence of residual disease but may also guide clinicians to stratify and manage these patients better,1 said Leonard Wartofsky, MD, during an Expo Theater presentation at the American Thyroid Association 87th Annual Meeting in Victoria, BC, Canada. Dr. Wartofsky is chairman emeritus of the department of medicine at MedStar Washington Hospital Center and professor of medicine at Georgetown University Hospital in Washington, DC.

Dr. Wartofsky discussed the principles of using the thyroglobulin (Tg) assay for risk stratification in the management of thyroid cancer

“In general if thyroglobulin is undetectable, that is a favorable sign that the surgery has been curative, and no further intervention is needed,” Dr. Wartofsky told EndocrineWeb, “However, choosing the right assay is crucial.”

Differentiating Between Tg Assays

Two types of Tg assays are used — competitive radioimmunoassay (RIA) and sandwich immunometric assays. The ideal approach is to first test for thyroglobulin (Tg) antibody because it can interfere with sandwich assays, such as immunochemiluminescent assays (ICMA). If Tg antibody is present, RIA should be used to measure serum Tg levels. Tg antibodies are seen in roughly a quarter to a third of thyroid cancer patients. RIA is more expensive and more time-consuming, though and isn’t performed in all laboratories.

“When antibodies are negative, more routine assays such as ICMA or immunoradiometric assays (IRMA), can be used without risk of interference from antibodies,” said Dr. Warofsky. The advantage of these assays is that they are automated in most commercial laboratories and have a quick turnaround time.1 The results are valid as long as there are no antibodies. In practice though, antibody testing and ICMA/IRMA for thyroglobulin are run together, he said. However, if the antibody results are positive, an RIA would need to be performed. Endocrinologists ought to be aware of which methods are used by their laboratory, he said.

“Most labs run the immunometric thyroglobulin assay (sandwich) and a thyroglobulin antibody at the same time. If the Tg antibody is positive, undetectable ICMA Tg is unreliable,” said Bryan Haugen, MD, professor of medicine and pathology and Mary Rossick Kern and Jerome H Kern Chair in Endocrine Neoplasms Research at the University of Colorado School of Medicine in Aurora, Colorado.

“The clinician needs to determine if the patient is low enough risk just to monitor the Tg antibody titer over time or send for the RIA assay,” Dr. Haugen told EndocrineWeb.

For Assays, It’s All In the Timing

“The timing for capturing a Tg measurement is just as important as selecting the right assay because Tg can circulate in the bloodstream for 10-12 days after surgery,” Dr. Wartofsky said. If testing is done too soon, the question may be—are you measuring leftover thyroglobulin from the thyroid gland or is it a residual tumor? The best time to test for Tg is about a month after surgery.1

Thyroglobulin levels following surgery are often the best indicator of residual tumor,1 according to Dr. Wartofsky. This is particularly true when performed with TSH stimulation, he said, because thyroid stimulating hormone (TSH) produces thyroglobulin release, “the way to really prove that a patient is cured is to do a provocative stimulation test, raising the TSH level to sky-high levels,” he said, and any remaining cancer cells will be stimulated to release thyroglobulin.1

“An undetectable thyroglobulin level when the TSH is low or suppressed is good news and we can reassure the patient that they are likely cured. But if it’s undetectable when they’re stimulated, that’s great news,” Dr. Wartofsky said.

How Long Should Patients Be Followed?

How long Tg should be measured will depend on the patient and their clinical picture, both Dr. Wartofsky and Dr. Haugen agreed.

“This is left to clinical judgment as to how and how long to follow a thyroid cancer patient,” said Dr. Wartofsky, “In general if the thyroglobulin is undetectable, no further intervention is necessary. But that is taken in the context of the original staging of the tumor. The size of the tumor, tender lymph node involvement, and the original staging also go into decisions about monitoring patients. All of those things are taken into consideration. So thyroglobulin is just one additional marker that is helpful to the endocrinologist to decide what the next step should be.”

Dr. Haugen added, “the interval and length of time that a Tg level needs to be done depends on the patient’s original stage/recurrence risk and subsequent response to therapy.” Typically for a low to intermediate risk patient who has an excellent response to therapy, Tg is measured following six to 12 months on levothyroxine, then the interval is increased. “We are following some thyroid cancer patients with Tg levels every 5 years,” he said.

Even patients with no detectable Tg at one year may require monitoring, said Dr. Wartofsky, which isn’t a problem since they are already being monitored for the purpose of their thyroid hormone replacement therapy so Tg may be measured once annually along with TSH.1

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